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1Conceptos Básicos y Marco Regional para la Validación de Software
2Conceptos Básicos y Marco Regional para la Validación de Software
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3Conceptos Básicos y Marco Regional para la Validación de Software
World’s changes
The Pharmaceutical Industry has adapted its business model in response to growing industry constraints and the decline of the primary-care focused blockbuster therapy.
Principal Key Success Factors of success in this “scenario” are:
Maintaining Quality
Optimising Process
Cost Management
Reducing Time to Market
Optimising Supply Chain
Latino America Consultores, with its experience, is one of the most Qualified Partners in South America to achieve that goal, according to cGMP requirements, with a special focus on Pharmaceutical Business Evolution.
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International Support
Momentum Life Science™
Support in R&D
Engineering, Design & Construction Support
Qualification, Validation & Management
Technology Transfer
IT in Compliance
Business Development & Alliance
Regulatory Affairs
Quality in Outsourcing & Auditing
Training
Business Process Re-engineering
Feasibility Studies
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Product Knowledge
Product & Process Support Supports for Formulation, Pilot Phases, Scale Up and Industrialization Process Qualification Technology Transfer Support
Regulatory Affairs & Compliance International Regulatory Support Supports in Preparation Dossiers Supports in Preparation of Technical File for Medical Devices Preparation and Implementation of Variation Procedures
Engineering
Project: URS, Feasibility, Preliminary Budgeting, Conceptual Design, Basic Design, Detailed Design, Design Qualification
Verification: Equipment & Plant Qualification Support, Utilities Qualification Support, Analytical Methods & Equipment Qualification, Information & Data Management System Validation
Compliance, Innovation & Data ManagementERP, LIMS, DCS, SCADA, WMS, EDMS have to be in Compliance.
Feasibility Study & Software & Supplier Selection
Solution Providing & System Integration Support
Computer System Validation (GAMP 5.0), 21 CFR 11 Compliance
GxP Risk Assessment & Remediation Plan Management
Support for IT Infrastructure Management & Enhancement, Networks Qualification
Legacy System Assessment & Full Plant Remediation Support
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Computer System ValidationBasic Principles,
International References
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1. “Validación es la recopilación y documentación de evidencias suficientes para dar certeza razonable, dado el estado de la ciencia, que el proceso en consideración opera, y / u operará, según lo esperado” (B. Loftus, Process Validation - The Regulatory View, Proceedings of the Proprietary Association, 1979 Manufacturing Controls Seminary)
2. “Validación es establecer evidencia documentada la cual proporciona un alto grado de certeza que un proceso especifico producirá consistentemente un producto que cumpla las especificaciones y características de calidad predeterminadas” (FDA Guideline on General Principles of Validation, 1987)
3. La validación es una estrategia definida de prácticas y procedimientos inter-relacionados que en combinación con métodos de producción de rutina y técnicas de control de calidad ofrece garantía documentada de que un sistema está funcionando como se pretende de manera repetitiva y / o que un producto cumple con las especificaciones predeterminadas. (PDA TM#1 revised, Draft 13, Glossary)
Validación: DEFINICIÓN
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The GAP between manufacturer's “good intention” and low number of examined products could be supported and justified by validation
Validation ”says”…… “it’s working constantly under specification”
Could be Applied to preliminarily examination & scheduling of process details & to test and demonstrate that process is working properly
Efficacy of a well performed validation is underlined by the automatic reduction of production defects, waste … Plant Projects errors or re-work reduction
Whatever the Process could be validation ask the same: “demonstrate… & document objectively the proper functioning”
…. Why Validation?
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Principle
The introduction of computerised systems into systemsof manufacturing, including storage, distribution andquality control does not alter the need to observe therelevant principles given elsewhere in the Guide.
Where a computerised system replaces a manualoperation, there should be no resultant decrease inproduct quality or quality assurance.
Consideration should be given to the risk of losingaspects of the previous system which could result fromreducing the involvement of operators.
The Starting Point
Annex 11 EU GMP
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Functional Correctness (During Usage)
Data Correctness (enforced after 21 CFR Part 11) Accuracy
Validity
Availability
Confidentiality
Risk Management (enforced after FDA guidelines of 2004)
Computerised Systems – Regulatory Req.
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The Scenario
The Regulatory Reference (regulatory scenario) for Pharmaceutical will see different “actors” :
Regulatory Agency (INAME, ANVISA, INVIMA, FDA, EMA, PIC/S, ICH …)
Standard Agency/Association (ISO, BSI, …)
Industrial Associations (ISPE, PDA, GAMP, …)
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… are classifiable in:
Rules, emitted by Health Authority (Code of Federal Regulations, EU Directives, …)
Guide Lines for Inspections (FDA, PIC/S, ICH, …)
Guide line for Developments and Construction, Validation & Compliance of Plant, Equipments & Systems (ISPE, PDA, …)
Technical Rules & Standards (ISO 17799 / BSI 7799, …)
The Scenario - Documents
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… Not only 21 CFR Part 11
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USA and OUT of USA
Compliance and 21 CFR Part 11 is a Legal requisite to sell in USA
USA market represent value 50-60% of World’s Market
PIC/S Guidance PI 011
“Good practices for computerised systems in regulated “GxP” environment”
European Union EMA
Annex 11 (old version)
New Annex 11 (2011)
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REGIONAL REGULATIONS
CSV Local Regulations
Argentina Regulations Brasil Regulations Colombia Regulations Mexico Regulations
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ARGENTINA REGULATIONS
Disposición ANMAT Nº 2819/2004 (con las modificaciones de la Disp. ANMAT Nº 4844/2005) – OMS informe 32 (1995)Buenas Prácticas de Fabricación para Elaboradores, Importadores / Exportadores de Medicamentos.
4. CALIFICACIÓN Y VALIDACIÓN
4.11 Es de importancia crítica prestar particular atención a la validación de métodos analíticos de ensayo, sistemas automatizados y procedimientos de limpieza.
MINISTERIO DE SALUDAdministración Nacional de Medicamentos, Alimentos y Tecnología Médica
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COLOMBIA REGULATIONS
21. PROCESAMIENTO ELECTRÓNICO DE DATOS (INFORMÁTICA)21.1 ¿Existe un sistema de procesamiento y registro electrónico de datos? Informativo21.2 ¿Existen personas capacitadas responsables y autorizadas para el acceso al sistema (entrada de datos, consultas y modificaciones)? Crítico21.3 ¿Hay un procedimiento validado que indique las medidas a tomar en caso de una falla del sistema? Crítico21.4 ¿Existe un procedimiento de seguridad que únicamente permita el acceso de personal autorizado al sistema? Crítico21.5 ¿Se editan los datos y archivan en el historial del lote? Informativo21.6 ¿Son de fácil acceso y disponibilidad por parte del personal autorizado los datos correspondientes al registro de producción de cada lote? Crítico21.7 ¿Se tiene grabación de reserva de los registros de la información archivados electrónicamente? Crítico21.8 ¿Está convenientemente almacenada esta información? Crítico21.9 ¿Existe un procedimiento escrito para los casos de emergencia?
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BRASIL REGULATIONS
Current RegulationAgência Nacional de Vigilância SanitáriaResolução - RDC nº 17, de 16 de abril de 2010
Reference WHO Technical Reports 908 –
WHA Report 37 – 2003
Sistemas Computarizados Titulo VII SISTEMAS DE
INFORMAÇÃOCOMPUTADORIZADOS
GUIA DE VALIDAÇÃO DESISTEMASCOMPUTADORIZADOS
ANVISA
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Mexican REGULATIONS
14.6.1 Deben validarse los sistemas yaplicaciones computacionales relacionadoscon:
14.6.1.1 Transferencias de insumos yproducto.
14.6.1.2 Disposición de insumos y producto.
14.6.1.3 Control de procesos y análisis.
14.6.1.4 Control de sistemas críticos.
14.6.4 Registros y firmas electrónicas Audit Trail Firmas Electrónicas Registros Electrónicos
NOM-059-SSA1-2006
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Computer System ValidationFDA - 21 CFR part 11
EMA - GMP - Annex 11
PIC/S
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21 CRF Part 11
Rules were written for a “paper world”
Rules asks hand-written signatures
Technology has been made “Obsolete” rules for many aspects
Computerized Systems could provide big advantage to Pharmaceutical & regulated Industries
… Industry asks itself to verify with regulatory agency the permission to utilize Electronic Signatures
Electronic Record &Electronic Signature Management
Part 11--ELECTRONIC RECORDS; ELECTRONIC SIGNATURES
Subpart A--General Provisions
11.1 Scope.
11.2 Implementation.
11.3 Definitions.
Subpart B--Electronic Records
11.10 Controls for closed systems.
11.30 Controls for open systems.
11.50 Signature manifestations.
11.70 Signature/record binding.
Subpart C--Electronic Signature
11.100 General requirements.
11.200 Identification mechanisms and controls.
11.300 Controls for identification codes/passwords.
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21 CRF Part 11 – ER Key Points
Validation
Accurate and complete copies
Protection of records
Limiting system access
Secure audit trails
Operational system checks
Authority checks
Validity of source Training and experience
Policies and procedures defining responsibilities
Control over system documentation
Signature manifestation
Signature/record linking
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Subpart B: Validation & Protection
Validation: Discerning invalid/altered records involves:
Ability to identify when changes were made
Who made the changes
Whether these changes were authorized
Protection:
Protection of records to ensure:
Accurate and Ready Retrieval
Throughout the records retention period
Ensure security of records by maintaining adequate backups and backup procedures
Companies should specify their retention periods
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Subpart B: System Access
To protect against unauthorized input, deletion or modification of data including user IDs
Right of entry on a “Need to do Basis”
Keys, ID cards, codes, terminal access
Authorized and documented
Key Issues Staff Changes, damage/loss, unavailable
codes, distribution lists
Records of attempted unauthorized access
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Subpart B: Audit Trails
Created by the system independently of operators
Must record date and time of entries and actions that create, modify or delete electronic records
Record changes must not obscure previous data
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Subpart C: E-Sigs
Unique signatures
Verified identity before allocation
Certification by user firm
Two distinct components - unless biometric
Use of components during sessions
Used by genuine owner
Administered to prevent fraud
Uniqueness of each combined ID and password
Periodic checking, recall or revision
Loss management
Transaction safeguards
Testing of devices
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Principle
The introduction of computerised systems intosystems of manufacturing, including storage,distribution and quality control does not alter theneed to observe the relevant principles givenelsewhere in the Guide.
Where a computerised system replacesa manual operation, there should be noresultant decrease in product quality orquality assurance.
Consideration should be given to the risk oflosing aspects of the previous system whichcould result from reducing the involvement ofoperators.
Annex 11 Computerised Systems
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New Annex 11
Maintain old principle with the introduction of Risk Based Approach
Define the validation of the application and qualification of IT infrastructure
Requirements organized as life cycle
More specific requirements
Basic requirements electronic signatures
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Implementation of computerised systems The structure and functions of the computer system(s) Planning and life-cycle management Management and responsibilities User requirement specifications (URS) Functional specifications (FS) Suppliers, software developers and quality
management Important QMS and software standards attributes Testing Validation strategies and priorities GAMP validation approach based on different
categories of software products Retrospective validation
PI 011 – Key Elements
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Computer System ValidationGAMP® 5
Introduction
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GAMP Good Practice Guides
One of the Answer: GAMP Guides
GAMP® 5
Validation of LaboratoryComputerized Systems
Risk-Based Approach toElectronic Records & Signatures
Calibration Management
Validation of ProcessControl Systems
Validation of Legacy Systems
IT Infrastructure Control andCompliance
Global Information SystemsControl and Compliance
Testing of GxP Systems
Electronic Data Archiving
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Process Control: DCS, SCADA, MES (Manufacturing Execution
Systems), HVAC, Dispensing
Application: ERP, DSS (Decision Support System),
Regulatory eCTD, Document Management System
Laboratory LIMS, CDAS, Software for Instrument
Infrastructure: Network, Basic Software, Domain,
Notification System, Virtualisation
GAMP® 5 – Scope & Application
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GAMP® 5 – ACCEPTANCE
Acceptance of GAMP Guidance by regulators worldwide
Widespread incorporation of concepts and methods into policies and procedures of manufacturing companies worldwide
Many suppliers have adopted GAMP as the cornerstone of their quality systems
Covers “good practice” not just a compliance guide
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ICH Q9 Quality Risk Management
Good alignment with current GAMP riskapproach and strategic direction
Q9 adopted as overall framework for riskmanagement approach in GAMP 5
Impact of Q8 and forthcoming Q10 ISPE Product Quality Lifecycle Implementation
(PQLI) Initiative Practical Implementation of ICH Guidance and
Quality by Design ASTM Standards e.g. ASTM E2500 Standard Guide for
Specification, Design, and Verification ofPharmaceutical and BiopharmaceuticalManufacturing Systems and Equipment
GAMP® 5 – ALLIGNMENT
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From System Risk Based Approachto Process Risk Based Approach
A computerized system is considered as acomponent of a wider system &/or process,especially in an Integrated “Quality by Design”Environment
A Computer System Validation Separated byProcess Validation could be not anymorenecessary (& sometimes inconsistent)
GAMP5 encourage adopting an IntegratedApproach
GAMP® 5 – EVOLUTION
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1. Product & Process Knowledge
2. Integrated Life Cycle Approach in a QMS Environment
3. Flexible & Scalable Life Cycle Activities
4. Quality Risk Management
5. Maximize Supplier Involvement & participation
GAMP® 5 – KEY CONCEPT
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GAMP® 5 – SOFTWARE CATHEGORIES
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M1 Validation Planning
M2 Supplier Assessment
M3 Science Based Quality Risk Management
M4 Categories of Software and Hardware
M5 Design Review and Traceability
M6 Supplier Quality and Project Planning
M7 Validation Reporting
M8 Project Change and Configuration Management
M9 Document Management
M10 System Retirement (*)
GAMP® 5 – MANAGEMENT APPENDICES
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D1 User Requirements Specifications
D2 Functional Specifications
D3 Configuration and Design
D4 Management, Development, and Review of Software
D5 Testing of Computerized Systems
D6 System Descriptions (*)
D7 Data Migration (*)
GAMP® 5 – DEVELOPMENT APPENDICES
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GAMP® 5 – USING GAMP®5
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GAMP® 5 – BASIC APPROACH
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GAMP® 5 – LIFE CYCLE PHASES
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GAMP® 5 – NON CONFIGURED SYSTEMS
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GAMP® 5 – CONFIGURABLE SYSTEMS
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GAMP® 5 – CUSTOM SYSTEMS
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Computer System ValidationUse of
Risk Assessment
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Full Assessment – Metodology
DELIVERABLES
Prj.Planning&
Inventory
1
SystemsList
GMP&
Risk Assessment
2
Activity
Assessment21 CFR Part 11
3
GapAnalysis
4
Planning
5
Risk Assessment
Report
SystemAssessment
Report
GapAnalysisReport
ActionPlan
RemediationPlan
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La metodología del Análisis se aplica de acuerdo con los siguientes pasos:
1. Mapeo de Procesos (GxP)2. Identificación de Funciones Criticas3. Identificación del Escenario de riesgo4. Evaluación de probabilidad5. Evaluación de severidad del impacto6. Asignación de clasificación al riesgo7. Evaluación de la probabilidad de detección8. Asignación de prioridad al riesgo
El riesgo está basado en la identificación de un “Evento o Escenario de Riesgo”. Para cada amenaza al sistema, se identifica un posible evento de riesgo, relacionado con una operación-no correcta y/o una potencial corrupción o incumplimiento GxP de los datos que se manejan. Los posibles eventos relacionados a un mal funcionamiento del sistema se listan en el Risk Assessment Report.A cada riesgo se asocia una acción correctiva que va a impactar en la validación del sistema.
Using Risk Based Approach
METODOLOGÍA DEL ANÁLISIS DE RIESGO
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Computer System ValidationExample of Suggested Activity
&
Deliverables Structures
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RA - Risk Assessment
VP Validation
PLAN
TM Traceability
Matrix
FRS Functional Requirements Specifications
SDS System Design
Specifications
IQInstallation
Qualification
OQOperational Qualification
RA Datasheet RA Report
(RAR – CA) Collected Lists &
Documents
RA Results Scope , Objectives Roles &
Responsibility Activities &
Deliverables Criteria Management
Issues Draft Scheduling
RAR CA Type Description Owner Status Reporting/TO
DO PLAN
FRS ref . & IQ CODE Scope &
Description Test Conditions Expect. Results Collected Result Report
Main Document User’s Process Flow, & Blue
Print Manuals Implementation Project
Documents Configuration Docs Customization Docs User’s SOP, Application
Manuals
PQPerformances Qualification
Process Item / Process Flow Id. Process
Description Scope of Test &
Description Test Conditions Expect. Results Collected Result Report
System general architecture Equipment Technical
Datasheet System’s SOP Standard installation reports System Installed components System environment’s IT Working instruction & rules
System Risk Based Assessment& Remediation Planning/Controls System Description System Testing
SDS ref. & IQ CODE Scope &
Description Test Conditions Expect. Results Collected Result Report
DOC Hierarchy
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Comply International Rules show Innovation,Knowledge & affordability, and it’s a PowerfulBusiness Item
Design an Qualifying Process & Plant incompliance with FDA or EMA requirements,means that the Product, once ready to export, arecompatible with the most restrictive internationalrules;
A structure prepared to manage qualified processmeans reduction of Technology Transfer Time ,both IN & OUT;
An Integrated QMS, supported by QualifiedProcesses & Systems, reduce Inspection Risksand Inspection Preparation Time;
Qualified Processes means reduction ofRegistration Time
A Full Compliant Plant increase Group Trust andGroup Visibility
Benefit of Compliance
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Muchas Gracias por su Atención
Leandro Mbarakleandro.mbarak@latconsultores.com.arwww.latconsultores.com.ar
Gilberto Rossigilberto.rossi@latconsultores.com.arwww.latconsultores.com.ar